1. Field of the Invention
The invention in the field of cell biology, physiology and medicine relates to purified mammalian adipogenic proteins, genetic constructs thereof, antibodies thereto, and methods of using such factors to determine susceptibility to obesity and for evaluating efficacy of anti-obesity drugs.
2. Description of the Background Art
Adipose differentiation of adipogenic cell lines is under the control of protein or glycoprotein factors called "adipogenic factors" which either trigger or stimulate the process of adipose differentiation. The isolation and Complete identification of adipogenic factors is important because of their role in turning on the differentiation program. Reports in the literature have disclosed that abnormal levels of circulating adipogenic factors exist in the blood of obese individuals (Lau, D. C. W. et al., (1984) Proc. 7th International Congress Endocrinology Excerpta Medica, p. 866).
Adipogenic factors have been found in fetal bovine serum and in human serum and plasma. Crude fetuin preparations have been shown to possess adipogenic activity that is heat sensitive and acid (pH 1) sensitive. The adipogenic activity was attributed to the fetuin itself (Gaillard, D. et al. (1985) Biochem. Biophys. Acta 846:185-191). There have been additional reports of bovine or human serum or plasma factors which provided little or no characterization of the physico-chemical properties of the factors (Meada, Y. Y. et al. (1980) Exp. Cell. Res. 126:99-107; Kuri-Harcuch, W. et al., (1978) Proc. Natl. Acad. Sci. U.S.A. 75:6107-6109; Serrero, G. et al. (1979), In: Hormone and Cell Culture, Cold Spring Harbor Conference on Cell Proliferation, Vol. 6, (R. Ross et al., eds.), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.); D. Gaillard et al. (1984) In Vitro Cell. Dev. Biol. 20:79-88; and G. Sypniewska et al. (1986) Int. J. Obesity 10:265-276).
Aproliferin, a factor purified from human plasma, is a 45 kDa protein (Weir, M. L. et al., Am. J. Physiol. (1982) 125:546-554) which induces loss of proliferative potential of 3T3-T proadipocytes. Based on its molecular weight and mode of action (Grimaldi, P. et al. (1982) EMBO J. 1:687-692), aproliferin is distinct from the adipogenic factors of the present invention. A heat labile, acid stable and protease stable active fraction has also been isolated from fetal calf serum (Grimaldi et al., supra). It appears likely that the active component is arachidonic acid, a fatty acid (Gaillard, D. et al. (1989) Biochem. J. 257:389-397).